Endotoxin-induced monocytic microparticles have contrasting effects on endothelial inflammatory responses
Autor: | Valery Combes, Babette B. Weksler, Amandine Bonhoure, Beryl Wen, Georges E. Grau, Pierre-Olivier Couraud |
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Přispěvatelé: | Vascular Immunology Unit, The University of Sydney, Division of Hematology and Oncology, Weill Medical College of Cornell University [New York], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This work was supported by grants from the National Health Medical Research Council # 570771, 571014, 1009914, 1028241 and the Rebecca L. Cooper Medical Research Foundation. The support of the University of Sydney Bridging Support Grant and funding from the Al Kerr Bequest, Sydney Medic al School is also gratefully acknowle, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), The University of Sydney [Sydney], Institut Cochin (UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Bos, Mireille |
Jazyk: | angličtina |
Rok vydání: | 2014 |
Předmět: |
Lipopolysaccharides
Physiology lcsh:Medicine Gene Expression Vascular permeability Matrix metalloproteinase Epithelium Monocytes Pathogenesis Spectrum Analysis Techniques Animal Cells Cell-Derived Microparticles Immune Physiology Molecular Cell Biology Medicine and Health Sciences lcsh:Science Cellular Stress Responses Multidisciplinary medicine.diagnostic_test Chemistry Brain Flow Cytometry Intercellular Adhesion Molecule-1 Cell biology Endothelial stem cell medicine.anatomical_structure Cell Processes Spectrophotometry Tumor necrosis factor alpha Cytophotometry Anatomy Cellular Types Cellular Structures and Organelles Intracellular Research Article Signal Transduction Cell Physiology Endothelium General Science & Technology Immune Cells Immunology Research and Analysis Methods Flow cytometry Cell Line medicine [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology RNA Messenger Inflammation Tumor Necrosis Factor-alpha Interleukin-6 lcsh:R Interleukin-8 Biology and Life Sciences Endothelial Cells Epithelial Cells Cell Biology Coculture Techniques Biological Tissue Membrane Trafficking lcsh:Q Clinical Immunology Cytometry |
Zdroj: | PLoS ONE PLoS ONE, Public Library of Science, 2014, 9 (3), pp.e91597. ⟨10.1371/journal.pone.0091597⟩ PLoS ONE, Public Library of Science, 2014, 9 (3), pp.e91597. 〈10.1371/journal.pone.0091597〉 PLoS ONE, Vol 9, Iss 3, p e91597 (2014) PLoS ONE, 2014, 9 (3), pp.e91597. ⟨10.1371/journal.pone.0091597⟩ |
ISSN: | 1932-6203 |
DOI: | 10.1371/journal.pone.0091597⟩ |
Popis: | International audience; Septic shock is a severe disease state characterised by the body's life threatening response to infection. Complex interactions between endothelial cells and circulating monocytes are responsible for microvasculature dysfunction contributing to the pathogenesis of this syndrome. Here, we intended to determine whether microparticles derived from activated monocytes contribute towards inflammatory processes and notably vascular permeability. We found that endotoxin stimulation of human monocytes enhances the release of microparticles of varying phenotypes and mRNA contents. Elevated numbers of LPS-induced monocytic microparticles (mMP) expressed CD54 and contained higher levels of transcripts for pro-inflammatory cytokines such as TNF, IL-6 and IL-8. Using a prothrombin time assay, a greater reduction in plasma coagulation time was observed with LPS-induced mMP than with non-stimulated mMP. Co-incubation of mMP with the human brain endothelial cell line hCMEC/D3 triggered their time-dependent uptake and significantly enhanced endothelial microparticle release. Unexpectedly, mMP also modified signalling pathways by diminishing pSrc (tyr416) expression and promoted endothelial monolayer tightness, as demonstrated by endothelial impedance and permeability assays. Altogether, these data strongly suggest that LPS-induced mMP have contrasting effects on the intercellular communication network and display a dual potential: enhanced pro-inflammatory and procoagulant properties, together with protective function of the endothelium. |
Databáze: | OpenAIRE |
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